Bottom Line:
Biomaterial matrices are commonly used in conjunction with MSCs to aid cell delivery and support chondrogenic differentiation, functional extracellular matrix formation and three-dimensional tissue development.A number of specific transplantation protocols have successfully resurfaced articular cartilage in animals and humans to date.This will allow for further optimization of MSC proliferation, chondrogenic differentiation, bioengineered cartilage integration, and clinical outcome.

ABSTRACTArticular cartilage has a limited capacity to repair following injury. Early intervention is required to prevent progression of focal traumatic chondral and osteochondral defects to advanced cartilage degeneration and osteoarthritis. Novel cell-based tissue engineering techniques have been proposed with the goal of resurfacing defects with bioengineered tissue that recapitulates the properties of hyaline cartilage and integrates into native tissue. Transplantation of mesenchymal stem cells (MSCs) is a promising strategy given the high proliferative capacity of MSCs and their potential to differentiate into cartilage-producing cells - chondrocytes. MSCs are historically harvested through bone marrow aspiration, which does not require invasive surgical intervention or cartilage extraction from other sites as required by other cell-based strategies. Biomaterial matrices are commonly used in conjunction with MSCs to aid cell delivery and support chondrogenic differentiation, functional extracellular matrix formation and three-dimensional tissue development. A number of specific transplantation protocols have successfully resurfaced articular cartilage in animals and humans to date. In the clinical literature, MSC-seeded scaffolds have filled a majority of defects with integrated hyaline-like cartilage repair tissue based on arthroscopic, histologic and imaging assessment. Positive functional outcomes have been reported at 12 to 48 months post-implantation, but future work is required to assess long-term outcomes with respect to other treatment modalities. Despite relatively positive outcomes, further investigation is required to establish a consensus on techniques for treatment of chondral and osteochondral defects with respect to cell source, isolation and expansion, implantation density, in vitro precultivation, and scaffold composition. This will allow for further optimization of MSC proliferation, chondrogenic differentiation, bioengineered cartilage integration, and clinical outcome.

Mentions:
A comprehensive literature search was performed of MEDLINE, EMBASE and Web of Science databases to identify English articles published between 1994 and 2014 using various combinations of the following keywords: mesenchymal stem cell, stromal cell, bone marrow cell, cartilage, chondrogenesis, transplantation, in vitro, ex vivo, monolayer, cell aggregate, pellet, micromass, hydrogel, explant, in vivo, animal, rat, rabbit, dog, sheep, horse, pig, goat, murine, leporine, canine, ovine, equine, porcine, caprine, and human. Search steps performed within each database specifically for in vitro, in vivo animal and clinical literature are detailed in Additional file 1. Compilation of database outputs produced 6,137, 2,603 and 2,528 publications, respectively, for these searches. In vivo articles were then screened and included if they met the following criteria: (1) publication in English between 1994 and 2014; (2) clinical design with Oxford Centre for Evidence-Based Medicine 2011 level of evidence I to IV [27] or controlled animal design; and (3) assessment of MSC-based treatment of in vivo traumatic (natural or simulated), focal chondral or osteochondral defects. Relevant articles found within reference lists and within the journal Cartilage were also screened and considered for inclusion. This process yielded 36 pre-clinical in vivo animal studies, including 21 small animal and 15 large animal studies, and 15 clinical studies (Figure 1). Only key in vitro articles were included in our review as several hundred relevant articles were found within our initial search.Figure 1

Mentions:
A comprehensive literature search was performed of MEDLINE, EMBASE and Web of Science databases to identify English articles published between 1994 and 2014 using various combinations of the following keywords: mesenchymal stem cell, stromal cell, bone marrow cell, cartilage, chondrogenesis, transplantation, in vitro, ex vivo, monolayer, cell aggregate, pellet, micromass, hydrogel, explant, in vivo, animal, rat, rabbit, dog, sheep, horse, pig, goat, murine, leporine, canine, ovine, equine, porcine, caprine, and human. Search steps performed within each database specifically for in vitro, in vivo animal and clinical literature are detailed in Additional file 1. Compilation of database outputs produced 6,137, 2,603 and 2,528 publications, respectively, for these searches. In vivo articles were then screened and included if they met the following criteria: (1) publication in English between 1994 and 2014; (2) clinical design with Oxford Centre for Evidence-Based Medicine 2011 level of evidence I to IV [27] or controlled animal design; and (3) assessment of MSC-based treatment of in vivo traumatic (natural or simulated), focal chondral or osteochondral defects. Relevant articles found within reference lists and within the journal Cartilage were also screened and considered for inclusion. This process yielded 36 pre-clinical in vivo animal studies, including 21 small animal and 15 large animal studies, and 15 clinical studies (Figure 1). Only key in vitro articles were included in our review as several hundred relevant articles were found within our initial search.Figure 1

Bottom Line:
Biomaterial matrices are commonly used in conjunction with MSCs to aid cell delivery and support chondrogenic differentiation, functional extracellular matrix formation and three-dimensional tissue development.A number of specific transplantation protocols have successfully resurfaced articular cartilage in animals and humans to date.This will allow for further optimization of MSC proliferation, chondrogenic differentiation, bioengineered cartilage integration, and clinical outcome.

ABSTRACTArticular cartilage has a limited capacity to repair following injury. Early intervention is required to prevent progression of focal traumatic chondral and osteochondral defects to advanced cartilage degeneration and osteoarthritis. Novel cell-based tissue engineering techniques have been proposed with the goal of resurfacing defects with bioengineered tissue that recapitulates the properties of hyaline cartilage and integrates into native tissue. Transplantation of mesenchymal stem cells (MSCs) is a promising strategy given the high proliferative capacity of MSCs and their potential to differentiate into cartilage-producing cells - chondrocytes. MSCs are historically harvested through bone marrow aspiration, which does not require invasive surgical intervention or cartilage extraction from other sites as required by other cell-based strategies. Biomaterial matrices are commonly used in conjunction with MSCs to aid cell delivery and support chondrogenic differentiation, functional extracellular matrix formation and three-dimensional tissue development. A number of specific transplantation protocols have successfully resurfaced articular cartilage in animals and humans to date. In the clinical literature, MSC-seeded scaffolds have filled a majority of defects with integrated hyaline-like cartilage repair tissue based on arthroscopic, histologic and imaging assessment. Positive functional outcomes have been reported at 12 to 48 months post-implantation, but future work is required to assess long-term outcomes with respect to other treatment modalities. Despite relatively positive outcomes, further investigation is required to establish a consensus on techniques for treatment of chondral and osteochondral defects with respect to cell source, isolation and expansion, implantation density, in vitro precultivation, and scaffold composition. This will allow for further optimization of MSC proliferation, chondrogenic differentiation, bioengineered cartilage integration, and clinical outcome.